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1.
Drug Alcohol Depend. 2018 Apr 1;185:10-16. doi: 10.1016/j.drugalcdep.2017.11.035. Epub 2018 Feb 2.

Factors associated with sedative use and misuse among heroin users.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

BACKGROUND:

Rates of both opioid and sedative use and misuse are rising. Comorbid opioid and sedative use is associated with especially severe consequences (e.g., overdose and poor health outcomes). Heroin users report multiple motivations for sedative use, including self-medication. We aimed to understand differences in lifetime substance use characteristics between heroin users with different sedative use histories.

METHODS:

Substance use data were collected from 385 non-treatment seeking heroin users. Subjects were divided into four lifetime sedative-use groups: no use, medical use only, non-medical use only, and mixed medical and non-medical use. We examined patterns of use of various substances of abuse (tobacco, alcohol, marijuana, cocaine, heroin, and sedatives) and individual characteristics associated with each.

RESULTS:

Non-medical sedative use (alone or in addition to medical use) was associated with more negative consequences from using all substances. Medical sedative use alone was not related to increased overdose or emergency room visits associated with heroin use. Non-medical sedative use was associated with increases in 15 of the 21 measured heroin consequences and only one of those - health problems - was also associated with medical sedative use.

CONCLUSIONS:

Concomitant non-medical sedative use and heroin use is associated with significantly greater negative outcomes than those experienced by heroin users who report use of sedatives only as prescribed. Understanding these differences offers insight into risks related to using both substances and may help treatment providers create targeted harm reduction interventions for this population.

KEYWORDS:

Benzodiazepines; Consequences; Health outcomes; Heroin; Sedatives

PMID:
29413433
PMCID:
PMC5889740
[Available on 2019-04-01]
DOI:
10.1016/j.drugalcdep.2017.11.035
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2.
Addict Behav. 2018 Feb;77:260-266. doi: 10.1016/j.addbeh.2017.07.027. Epub 2017 Jul 22.

Developing a scale of domains of negative consequences of chronic heroin use.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA.
3
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; School of Social Work, Wayne State University, Detroit, MI 48201, USA.
4
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

BACKGROUND:

Chronic use of heroin typically leads to numerous negative life consequences and serious clinical impairment. Increased negative consequences can result in poor treatment outcomes as well as adverse health effects and impaired social functioning. Certain risk factors, including early substance use initiation, concurrent use of other illicit substances, and injection drug use are associated with an increase in negative consequences. This study examined whether there are unique domains of heroin consequences and, if so, whether these domains are related to specific substance use characteristics.

METHODS:

Data regarding substance use characteristics were collected from 370 non-treatment seeking, heroin-using, 18 to 55year-old participants from the Detroit metropolitan area. Principal component analysis (PCA) was used to analyze the factor structure of 21 negative heroin consequence items.

RESULTS:

PCA demonstrated that heroin consequences could be divided into 5 unique domains. These unique domains were related to specific substance use characteristics and heroin consequence domains. Injection heroin use was significantly associated with increased Factor 1 consequences (primarily acute medical problems) but not with consequences in other domains. Certain substance use characteristics, such as injection status and earlier onset of marijuana use, were associated with increased consequences in specific domains.

CONCLUSIONS:

These findings support the existence of unique domains of negative consequences, and indicate that some risk factors (e.g. injection use) may be specific to these domains. Potential tailored-treatment strategies aimed at improving treatment engagement and reducing harm for heroin use based on person-specific risks and negative consequences are discussed.

KEYWORDS:

Consequences; Harm reduction; Heroin; Injection; Scale development

PMID:
28756940
PMCID:
PMC5701874
[Available on 2019-02-01]
DOI:
10.1016/j.addbeh.2017.07.027
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3.
J Subst Abuse Treat. 2017 Jul;78:15-21. doi: 10.1016/j.jsat.2017.04.007. Epub 2017 Apr 14.

Baseline risk factors for drug use among African-American patients during first-month induction/stabilization on methadone.

Author information

1
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA; School of Social Work, Wayne State University, Detroit, MI, USA. Electronic address: jlister@wayne.edu.
2
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
3
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: dledgerw@med.wayne.edu.

Abstract

Drug use during methadone induction/stabilization negatively influences later methadone-maintenance-treatment [MMT] outcomes (retention, abstinence). Our study examined the association of baseline risk factors to drug use during the first month of methadone treatment as well as longer-term treatment retention. We conducted these analyses among a race/ethnic minority group at high risk for worse MMT outcomes. African-American MMT patients (N=212) were interviewed at intake to assess clinical (drug use history), psychosocial (close family member substance abuse, psychosocial problems), and demographic factors. Outcomes were first-month opioid+ and cocaine+ urine drug screen [UDS] results and retention (days in treatment). In bivariate analyses, co-occurring cocaine abuse/dependence was associated with worse outcomes for opioid+ UDS, cocaine+ UDS, and retention. Being a primary injection opioid user and residing farther from the clinic were associated with a higher proportion of cocaine+ UDS and shorter retention, respectively. Patients with a significant other substance abuse history provided a higher proportion of both opioid+ and cocaine+ UDS. Sibling and parent substance abuse histories were associated with a higher proportion of opioid+ UDS and shorter retention. Psychosocial problems (economic, housing) were associated with a higher proportion of cocaine+ UDS. In multivariate analyses, co-occurring cocaine abuse/dependence and primary injection opioid use best accounted for first-month opioid+ and cocaine+ UDS, respectively. A higher proportion of first-month opioid+ and cocaine+ UDS and living farther from the clinic accounted for retention. African-American patients reporting baseline risk factors (particularly clinical) experience worse short- and long-term MMT outcomes. Recommendations for improving standards of care are discussed.

KEYWORDS:

African-American; Cocaine; Heroin; Methadone maintenance treatment; Minority health

PMID:
28554598
DOI:
10.1016/j.jsat.2017.04.007
[Indexed for MEDLINE]
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4.
Neuropharmacology. 2017 May 15;118:38-45. doi: 10.1016/j.neuropharm.2017.03.005. Epub 2017 Mar 7.

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

Author information

1
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States. Electronic address: jacksonab2@mymail.vcu.edu.
2
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States; Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey.
3
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
4
Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC, United States.
5
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2761 East Jefferson Ave., Detroit, MI 48207, United States.

Abstract

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence.

KEYWORDS:

Behavioral pharmacology; Mice; Nicotine dependence

PMID:
28279662
PMCID:
PMC5410388
DOI:
10.1016/j.neuropharm.2017.03.005
[Indexed for MEDLINE]
Free PMC Article
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5.
J Subst Abuse Treat. 2017 Apr;75:17-21. doi: 10.1016/j.jsat.2017.01.004. Epub 2017 Jan 14.

Characterizing fentanyl use in methadone-maintained clients.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA. Electronic address: cynthia.arfken@wayne.edu.
2
School of Medicine, Wayne State University, Detroit, MI 48201, USA.
3
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.

Abstract

AIMS:

Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl.

METHODS:

A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey.

RESULTS:

Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (p<0.05) more likely to use cocaine, have multiple treatment admissions to the clinic, and leave treatment sooner. Fentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine.

CONCLUSIONS:

Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed.

KEYWORDS:

Cocaine; Fentanyl; Methadone maintenance; Urine drug screens

PMID:
28237050
DOI:
10.1016/j.jsat.2017.01.004
[Indexed for MEDLINE]
Icon for Elsevier Science
6.
Drug Alcohol Depend. 2016 Sep 1;166:143-9. doi: 10.1016/j.drugalcdep.2016.07.004. Epub 2016 Jul 18.

Magnitude and duration of cue-induced craving for marijuana in volunteers with cannabis use disorder.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine,Wayne State University, Detroit, MI 48201, USA. Electronic address: llundahl@med.wayne.edu.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine,Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.

Abstract

AIMS:

Evaluate magnitude and duration of subjective and physiologic responses to neutral and marijuana (MJ)-related cues in cannabis dependent volunteers.

METHODS:

33 volunteers (17 male) who met DSM-IV criteria for Cannabis Abuse or Dependence were exposed to neutral (first) then MJ-related visual, auditory, olfactory and tactile cues. Mood, drug craving and physiology were assessed at baseline, post-neutral, post-MJ and 15-min post MJ cue exposure to determine magnitude of cue- responses. For a subset of participants (n=15; 9 male), measures of craving and physiology were collected also at 30-, 90-, and 150-min post-MJ cue to examine duration of cue-effects.

RESULTS:

In cue-response magnitude analyses, visual analog scale (VAS) items craving for, urge to use, and desire to smoke MJ, Total and Compulsivity subscale scores of the Marijuana Craving Questionnaire, anxiety ratings, and diastolic blood pressure (BP) were significantly elevated following MJ vs. neutral cue exposure. In cue-response duration analyses, desire and urge to use MJ remained significantly elevated at 30-, 90- and 150-min post MJ-cue exposure, relative to baseline and neutral cues.

CONCLUSIONS:

Presentation of polysensory MJ cues increased MJ craving, anxiety and diastolic BP relative to baseline and neutral cues. MJ craving remained elevated up to 150-min after MJ cue presentation. This finding confirms that carry-over effects from drug cue presentation must be considered in cue reactivity studies.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00218504 NCT00218478.

KEYWORDS:

Craving; Duration; Magnitude; Marijuana cue reactivity

PMID:
27436749
PMCID:
PMC5113710
DOI:
10.1016/j.drugalcdep.2016.07.004
[Indexed for MEDLINE]
Free PMC Article
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7.
Pediatr Clin North Am. 2016 Jun;63(3):425-46. doi: 10.1016/j.pcl.2016.02.001.

Behavioral Economic Factors Related to Pediatric Obesity.

Author information

1
Department of Family Medicine and Public Health Sciences, School of Medicine, iBio - Behavioral Health, Wayne State University, 6135 Woodward, H206, Detroit, MI 48202, USA. Electronic address: atiura@med.wayne.edu.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, iBio -Behavioral Health, Wayne State University, Tolan Park Medical Building, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy & Health Sciences, iBio -Behavioral Health, Wayne State University, Tolan Park Medical Building, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI 48201, USA.

Abstract

Behavioral economics (BE) suggests that food and activity choices are governed by costs, available alternatives, and reinforcement. This article reviews basic, translational, and intervention research using a BE framework with overweight or obese children up to age 18. We address BE concepts and methods, and discuss developmental issues, the continuum of BE intervention approaches, findings of studies focused on increasing the cost of unwanted behaviors (ie, energy-dense food intake and sedentary behavior) and decreasing the cost of desired behaviors (ie, healthy food intake and PA), and our team's recent basic behavioral studies using BE approaches with minority adolescents.

KEYWORDS:

Behavioral economics; Demand; Energy intake; Food reinforcement; Incentives; Obesity; Pediatric; Physical activity

PMID:
27261543
PMCID:
PMC4893960
DOI:
10.1016/j.pcl.2016.02.001
[Indexed for MEDLINE]
Free PMC Article
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8.
Drug Alcohol Depend. 2016 Jun 1;163:40-7. doi: 10.1016/j.drugalcdep.2016.03.018. Epub 2016 Mar 26.

A pilot randomized clinical trial of an intervention to reduce overdose risk behaviors among emergency department patients at risk for prescription opioid overdose.

Author information

1
Department of Psychiatry, University of Michigan Medical School, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA; VA Center for Clinical Management Research (CCMR), Department of Veterans Affairs Healthcare System, 2800 Plymouth Rd., Bldg. 16, Ann Arbor, MI 48109, USA; University of Michigan Injury Center, University of Michigan Medical School, 2800 Plymouth Rd., Bldg. 10, Ann Arbor, MI 48109, USA; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Rd., Bldg. 16, Ann Arbor, MI 48109, USA. Electronic address: amybohne@med.umich.edu.
2
Department of Psychiatry, University of Michigan Medical School, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA.
3
University of Michigan Injury Center, University of Michigan Medical School, 2800 Plymouth Rd., Bldg. 10, Ann Arbor, MI 48109, USA; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Rd., Bldg. 16, Ann Arbor, MI 48109, USA; Department of Emergency Medicine, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA; Department of Health Behavior and Health Education, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
4
Department of Psychiatry and Behavioral Neurosciences, and Department of Pharmacy Practice, 3901Chrysler Service Drive, Suite 2A, Wayne State University, Detroit, MI 48201, USA.
5
Department of Psychiatry, University of Michigan Medical School, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA; VA Center for Clinical Management Research (CCMR), Department of Veterans Affairs Healthcare System, 2800 Plymouth Rd., Bldg. 16, Ann Arbor, MI 48109, USA.
6
Department of Psychiatry, University of Michigan Medical School, 4250 Plymouth Rd., Ann Arbor, MI 48109, USA; University of Michigan Injury Center, University of Michigan Medical School, 2800 Plymouth Rd., Bldg. 10, Ann Arbor, MI 48109, USA.

Abstract

BACKGROUND AND AIMS:

Prescription opioid overdose is a significant public health problem. Interventions to prevent overdose risk behaviors among high-risk patients are lacking. This study examined the impact of a motivational intervention to reduce opioid misuse and overdose risk behaviors.

METHODS:

This study was a pilot randomized controlled trial set in a single emergency department (ED) in which, 204 adult, English-speaking patients seeking care who reported prescription opioid misuse during the prior 3 months were recruited. Patients were randomized to either the intervention, a 30-minute motivational interviewing-based session delivered by a therapist plus educational enhanced usual care (EUC), or EUC alone. Participants completed self-reported surveys at baseline and 6 months post-baseline (87% retention rate) to measure the primary outcomes of overdose risk behaviors and the secondary outcome of non-medical opioid use.

FINDINGS:

Participants in the intervention condition reported significantly lower levels of overdose risk behaviors (incidence rate ratio [IRR]=0.72, 95% CI: 0.59-0.87; 40.5% reduction in mean vs. 14.7%) and lower levels of non-medical opioid use (IRR=0.81, 95% CI: 0.70-0.92; 50.0% reduction in mean vs. 39.5%) at follow-up compared to the EUC condition.

CONCLUSIONS:

This study represents the first clinical trial of a behavioral intervention to reduce overdose risk. Results indicate that this single motivational enhancement session reduced prescription opioid overdose risk behaviors, including opioid misuse, among adult patients in the ED.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01894087.

KEYWORDS:

Behavioral intervention; Overdose; Pain; Prescription opioids

[Indexed for MEDLINE]
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9.
Subst Abuse. 2016 Jan 11;9(Suppl 1):11-20. doi: 10.4137/SART.S22441. eCollection 2015.

Parental Support, Mental Health, and Alcohol and Marijuana Use in National and High-Risk African-American Adolescent Samples.

Author information

1
Department of Kinesiology and Health Education, Population Research Center, University of Texas, Austin, TX, USA.
2
Department of Psychology, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
3
College of Nursing, University of Massachusetts, Amherst, MA, USA.
4
Merrill Palmer Skillman Institute, Wayne State University, Detroit, MI, USA.; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
5
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.; Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA.
6
Department of Family Medicine, Wayne State University, Detroit, MI, USA.
7
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
8
Department of Pediatrics, Wayne State University, Detroit, MI, USA.

Abstract

African-American adolescents experience disproportionate rates of negative consequences of substance use despite using substances at average or below-average rates. Due to underrepresentation of African-American adolescents in etiological literature, risk and protective processes associated with their substance use require further study. This study examines the role of parental support in adolescents' conduct problems (CPs), depressive symptoms (DSs), and alcohol and marijuana use in a national sample and a high-risk sample of African-American adolescents. In both samples, parental support was inversely related to adolescent CPs, DSs, and alcohol and marijuana use. CPs, but not DSs, partially mediated the relation of parental support to substance use. Results were consistent across the national and high-risk samples, suggesting that the protective effect of parental support applies to African-American adolescents from a range of demographic backgrounds.

KEYWORDS:

African-American; alcohol; conduct problems; depressive symptoms; marijuana; parenting

10.
J Clin Psychopharmacol. 2016 Feb;36(1):18-26. doi: 10.1097/JCP.0000000000000434.

Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.

Author information

1
From *Indivior Inc., Richmond, VA; †the Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI; and ‡Vince & Associates Clinical Research, Inc., Overland Park, KS.

Abstract

A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder.

PMID:
26650971
PMCID:
PMC5549150
DOI:
10.1097/JCP.0000000000000434
[Indexed for MEDLINE]
Free PMC Article
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11.
Exp Clin Psychopharmacol. 2015 Dec;23(6):455-63. doi: 10.1037/pha0000054.

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine and Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.

Abstract

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

PMID:
26595426
PMCID:
PMC4661782
DOI:
10.1037/pha0000054
[Indexed for MEDLINE]
Free PMC Article
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12.
Psychiatry Res. 2015 Aug 30;233(2):218-24. doi: 10.1016/j.pscychresns.2015.07.002. Epub 2015 Jul 3.

Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo (1)H MRS study.

Author information

1
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, 3901 Chrysler Drive, Suite 2A, Detroit, MI 48201, USA; Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA. Electronic address: mgreen@med.wayne.edu.
2
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, 3901 Chrysler Drive, Suite 2A, Detroit, MI 48201, USA; Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.
3
Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.

Abstract

Mu-opioid receptor agonists alter brain glutamate (GLU) levels in laboratory animals. This clinical study used proton magnetic resonance spectroscopy ((1)H MRS) to examine regional brain GLU levels during experimental manipulation of methadone (MTD) maintenance dose under double-blind, within-subject conditions in seven heroin-dependent volunteers. Subjects were scanned first at a high MTD dose (100 mg/day), underwent a 3-week outpatient MTD dose taper, and then were scanned again at a low MTD dose (10-25 mg/day; modified for participant comfort). Five age- and cigarette smoking-matched controls were scanned once. In vivo short echo time (TE = 22 ms), single voxel (1)H MRS data from midline pregenual anterior cingulate cortex (ACC) and thalamus (4.5 cm(3) each) were collected using PRESS on a 4-Tesla MRI system. Absolute metabolite levels were quantified. GLU levels in the ACC, but not the thalamus, were higher at the low relative to the high MTD dose in heroin-dependent subjects. No other metabolites differed by MTD dose, or between control vs. heroin-dependent subjects (at either MTD dose). GLU levels in the ACC were inversely related to the duration of cigarette smoking (controls) and heroin use (experimental group). Future studies are warranted to investigate the relationship between GLU levels during treatment (and detoxification), and withdrawal symptoms or relapse.

KEYWORDS:

Detoxification; Dose taper; Neurochemistry; Opioid use disorder; Pharmacotherapy; Proton magnetic resonance spectroscopy

[Indexed for MEDLINE]
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13.
Am J Addict. 2015 Jun;24(4):329-35. doi: 10.1111/ajad.12187. Epub 2015 Apr 24.

Functional mu opioid receptor polymorphism (OPRM1 A(118) G) associated with heroin use outcomes in Caucasian males: A pilot study.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan; Translational Neuroscience Program, Wayne State University, Detroit, Michigan.

Abstract

BACKGROUND:

Heroin's analgesic, euphoric and dependence-producing effects are primarily mediated by the mu opioid receptor (MOR). A single gene, OPRM1, encodes the MOR. The functional polymorphism A(118)G, located in exon 1 of the OPRM1 gene, results in anatomically-specific reductions in MOR expression, which may alter an individual's response to heroin. In prior studies 118G (rare allele) carriers demonstrated significantly greater opioid tolerance, overdose vulnerability, and pain sensitivity than 118AA homozygotes. Those findings suggest OPRM1 genotype may impact characteristics of heroin use.

METHODS:

The present pilot study characterized the impact of OPRM1 genotype (rs1799971, 118G allele carriers vs. 118AA homozygotes) on heroin-use phenotypes associated with heroin dependence severity in a sample of male, Caucasian chronic heroin users (n = 86).

RESULTS:

Results indicate that 118G allele carriers reported significantly more heroin use-related consequences and heroin-quit attempts, and were more likely to have sought treatment for their heroin use than 118AA homozygotes.

CONCLUSIONS:

These preliminary findings, consistent with extant data, illustrate a role for OPRM1 allelic variation on heroin use characteristics, and provide support for considering genotype in heroin treatment and relapse prevention.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00218309 NCT00218361 NCT00608504 NCT00684840.

PMID:
25911999
PMCID:
PMC5541380
DOI:
10.1111/ajad.12187
[Indexed for MEDLINE]
Free PMC Article
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14.
J Subst Abuse Treat. 2015 Jul;54:37-43. doi: 10.1016/j.jsat.2015.01.009. Epub 2015 Jan 31.

Gender-specific predictors of retention and opioid abstinence during methadone maintenance treatment.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: levinea@uwindsor.ca.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: llundahl@med.wayne.edu.
3
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: dledgerw@med.wayne.edu.
4
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: mlisiesk@med.wayne.edu.
5
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: grhodes@med.wayne.edu.
6
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, 3901 Chrysler Service Drive, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

AIMS:

Retention in methadone maintenance treatment (MMT) for 1 year is associated with positive outcomes including opioid abstinence, however, most studies have not investigated gender differences. We hypothesized that predictors of retention and opioid abstinence would differ between men and women, and aimed to determine which factors best predict retention and abstinence for each gender.

METHODS:

Data were available for 290 patients (173 M, 117 F) admitted to outpatient MMT. Regression analyses, stratified by gender, were conducted to identify unique predictors of MMT retention (<1 vs. >1 year) and opioid abstinence rate (proportion of opioid-free urine samples up to 1 year retention).

RESULTS:

Gender did not significantly predict treatment retention (mean = 231 days, 39% retained > 1 year) or opioid abstinence (49% overall). For males, significant predictors of > 1-year retention were urine samples negative for opioids (odds ratio [OR] = 6.67) and cannabinoids (OR = 5.00) during the first month, and not cocaine dependent (OR = 2.70). Significant predictors of higher long-term opioid abstinence were first-month urine samples negative for opioids and cocaine metabolites. For females, significant predictors of >1-year retention were first-month urine samples negative for cocaine metabolites (OR = 4.00) and cannabinoids (OR = 9.26), and no history of sexual victimization (OR = 3.03). The only significant predictor of higher opioid abstinence rate was first-month opioid-free urine samples.

CONCLUSIONS:

These findings indicate gender-specific predictors of MMT retention and opioid abstinence. Future studies on MMT outcomes should examine each gender separately, and consider unique pathways by which females and males adhere to, and benefit from MMT.

KEYWORDS:

Abstinence; Gender; Methadone maintenance; Predictors; Retention; Treatment

PMID:
25795601
DOI:
10.1016/j.jsat.2015.01.009
[Indexed for MEDLINE]
Icon for Elsevier Science
15.
Addict Behav. 2015 Jun;45:287-93. doi: 10.1016/j.addbeh.2015.02.014. Epub 2015 Feb 26.

Progression to regular heroin use: examination of patterns, predictors, and consequences.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
3
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

BACKGROUND:

The present study retrospectively evaluated the chronology and predictors of substance use progression in current heroin-using individuals.

METHODS:

Out-of-treatment heroin users (urinalysis-verified; N=562) were screened for laboratory-based research studies using questionnaires and urinalysis. Comprehensive substance use histories were collected. Between- and within-substance use progression was analyzed using stepwise linear regression models.

RESULTS:

The strongest predictor of onset of regular heroin use was age at initial heroin use, accounting for 71.8% of variance. The strongest between-substance predictors of regular heroin use were ages at regular alcohol and tobacco use, accounting for 8.1% of variance. Earlier onset of regular heroin use (≤20 years) vs. older onset (≥30 years) was associated with a more rapid progression from initial to regular use, longer duration of heroin use, more lifetime use-related negative consequences, and greater likelihood of injecting heroin. The majority of participants (79.7%) reported substance use progression consistent with the gateway hypothesis. Gateway-inconsistent individuals were more likely to be African-American and to report younger age at initial use, longer duration of heroin use, and more frequent past-month heroin use.

CONCLUSIONS:

Our findings demonstrate the predictive validity and clinical relevance of evaluating substance use chronology and the gateway hypothesis pattern of progression.

KEYWORDS:

Gateway hypothesis; Heroin use disorder; Opioid; Substance use progression

PMID:
25765913
PMCID:
PMC5541382
DOI:
10.1016/j.addbeh.2015.02.014
[Indexed for MEDLINE]
Free PMC Article
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16.
Drug Alcohol Depend. 2015 Apr 1;149:187-93. doi: 10.1016/j.drugalcdep.2015.01.046. Epub 2015 Feb 11.

Effect of oral THC pretreatment on marijuana cue-induced responses in cannabis dependent volunteers.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA. Electronic address: llundahl@med.wayne.edu.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.

Abstract

BACKGROUND:

The current study tested whether oral Δ(9)-tetrahydrocannabinol (THC: 0-, 10-, and 20-mg) pretreatment would attenuate polysensory cue-induced craving for marijuana.

METHODS:

Cannabis dependent participants (7 males and 7 females, who smoked on average 5.4 ± 1.1 blunts daily) completed 3 experimental sessions (oral THC pretreatment dose; counterbalanced order) using a placebo-controlled within-subject crossover design. During each session, participants completed a baseline evaluation and were first exposed to neutral cues then marijuana cues while physiological measures and subjective ratings of mood, craving, and drug effect were recorded.

RESULTS:

Following placebo oral THC pretreatment, marijuana (vs. neutral) cues significantly increased ratings of marijuana craving (desire and urge to use, Marijuana Craving Questionnaire (MCQ)-Compulsivity scale), anxious mood and feeling hungry. Males also reported feeling more "Down" during marijuana cues relative to females. Pretreatment with oral THC (10-mg and/or 20-mg vs. placebo) significantly attenuated marijuana cue-induced increases in craving and anxiety but not hunger. Oral THC attenuation of the cue-induced increase in MCQ-Compulsivity ratings was observed in females only. Oral THC produced statistically (but not clinically) significant increases in heart rate and decreases in diastolic blood pressure, independent of cues.

CONCLUSIONS:

These marijuana-cue findings replicate earlier results and further demonstrate that oral THC can attenuate selected effects during marijuana multi-cue exposure, and that some of these effects may be sex-related. Results of this study suggest oral THC may be effective for reducing marijuana cue-elicited (conditioned) effects. Further study is needed to determine whether females may selectively benefit from oral THC for this purpose.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00218504.

KEYWORDS:

Cannabis dependence; Craving; Cues; Dronabinol; Marijuana; THC

[Indexed for MEDLINE]
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17.
Drug Alcohol Depend. 2015 Mar 1;148:217-20. doi: 10.1016/j.drugalcdep.2015.01.010. Epub 2015 Jan 19.

Exploration of the telescoping effect among not-in-treatment, intensive heroin-using research volunteers.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, and Wayne State University, Detroit, MI 48201, USA.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, and Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

BACKGROUND:

Addiction research literature suggests some demographic groups exhibit a later age of substance use initiation, more rapid escalation to dependence, and worse substance use-related outcomes. This 'telescoping' effect has been observed more often in females but has not yet been examined in not-in-treatment heroin users or racial subgroups.

METHODS:

Not-in-treatment, intensive heroin-using adults screened for laboratory-based research studies (N=554; range 18-55 yr; mean age: 42.5 yr; 60.5% African American [AA]; 70.2% male) were included in this secondary analysis. A comprehensive drug history questionnaire assessed heroin-use characteristics and lifetime adverse consequences. We examined telescoping effects by racial and gender groups: Caucasian males and females; AA males and females.

RESULTS:

Caucasian males initiated heroin use significantly later than AA males but this difference was not observed for age at intensive heroin use (≥3 times weekly). Caucasian males reported significantly more lifetime heroin use-related consequences, were more likely to inject heroin, and reported more-frequent past-month heroin use, but did not differ from AA males in lifetime heroin quit attempts or prior heroin treatment. Females, compared to males, reported later onset of initial and intensive use, but there was no gender-telescoping effect from initial to intensive heroin-use.

CONCLUSIONS:

In this not-in-treatment sample, Caucasian males exhibited more rapid heroin-use progression and adverse consequences than AA males, i.e., within-gender, racial-group telescoping. Despite later-onset heroin use among females, there was no evidence of gender-related telescoping. Given the resurgence of heroin use, differential heroin-use trajectories across demographic groups may be helpful in planning interventions.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00218309 NCT00218361 NCT00429767 NCT00608504 NCT00684840 NCT00698737 NCT01536925.

KEYWORDS:

Gender; Heroin; Race; Telescoping effect

PMID:
25630964
PMCID:
PMC5535755
DOI:
10.1016/j.drugalcdep.2015.01.010
[Indexed for MEDLINE]
Free PMC Article
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18.
Drug Alcohol Depend. 2015 Jan 1;146:89-96. doi: 10.1016/j.drugalcdep.2014.11.016. Epub 2014 Nov 26.

Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA.
2
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
3
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

BACKGROUND:

Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals' heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes.

METHODS:

Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly).

RESULTS:

Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 days vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper.

CONCLUSIONS:

Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes.

KEYWORDS:

Abstinence; Buprenorphine; Dose taper; Heroin; Maintenance; Relapse

PMID:
25479914
PMCID:
PMC4272885
DOI:
10.1016/j.drugalcdep.2014.11.016
[Indexed for MEDLINE]
Free PMC Article
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19.
Addict Behav. 2015 Feb;41:1-6. doi: 10.1016/j.addbeh.2014.09.017. Epub 2014 Sep 22.

Causal pathways between impulsiveness, cocaine use consequences, and depression.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA. Electronic address: jlister@med.wayne.edu.
2
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA. Electronic address: dledgerwood@med.wayne.edu.
3
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA. Electronic address: llundahl@med.wayne.edu.
4
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA; Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA. Electronic address: mgreen@med.wayne.edu.

Abstract

AIMS:

The present study examined whether lifetime cocaine use consequences mediate the relationship between trait impulsiveness and current depression symptoms among regular cocaine users.

METHODS:

Regular cocaine users (N=108) were assessed using: Barratt Impulsiveness Scale subscales (non-planning, attentional, motor sub-scales) to measure trait impulsiveness; a standardized Drug History and Use Questionnaire to measure cocaine use and related consequences; and Beck Depression Inventory to measure current depression symptoms.

RESULTS:

All impulsiveness subscales were positively associated with an earlier age of first cocaine use, a higher degree of current depression symptoms and a greater number of lifetime cocaine use consequences. In three separate simple mediation tests, lifetime cocaine use consequences partially mediated the relationship between each of the impulsiveness subscales (non-planning: R(2)=.42; attentional: R(2)=.40; motor: R(2)=.24) and current depression symptoms. Separate moderated mediation analyses failed to demonstrate an interaction between lifetime cocaine use and cocaine-related consequences predicting depression symptoms for the mediation models.

CONCLUSIONS:

Cocaine-related consequences function in a more nuanced manner than just an outcome of impulsiveness or cocaine use, but as a pathway between trait impulsiveness and current depression symptoms.

KEYWORDS:

Cocaine; Cocaine use consequences; Depression; Impulsiveness; Pathways

PMID:
25280245
PMCID:
PMC4252393
DOI:
10.1016/j.addbeh.2014.09.017
[Indexed for MEDLINE]
Free PMC Article
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20.
Drug Alcohol Depend. 2014 Nov 1;144:1-11. doi: 10.1016/j.drugalcdep.2014.07.035. Epub 2014 Aug 19.

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, School of Medicine, and Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Tolan Park Medical Building, Suite 2A, 3901 Chrysler Service Drive, Detroit, MI 48201, USA. Electronic address: mgreen@med.wayne.edu.
2
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
3
Department of Internal Medicine Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

BACKGROUND:

Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens.

METHODS:

We review scientific data concerning BUP-induced changes in μOR availability and their relationship to clinical efficacy.

RESULTS:

Withdrawal suppression appears to require ≤50% μOR availability, associated with BUP trough plasma concentrations ≥1 ng/mL; for most patients, this may require single daily BUP doses of 4 mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% μOR availability, associated with BUP trough plasma concentrations ≥3 ng/mL; for most individuals, this may require single daily BUP doses >16 mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% μOR availability would be required.

CONCLUSION:

For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted.

KEYWORDS:

Buprenorphine; Opioid dependence; Opioid receptors; Policy; Positron emission tomography; Treatment

PMID:
25179217
PMCID:
PMC4252738
DOI:
10.1016/j.drugalcdep.2014.07.035
[Indexed for MEDLINE]
Free PMC Article
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